Many pathological oral processes, ranging from periodontal disease to carcinoma, are associated with or are causally related to changes in the maintenance of epithelial structure. Information which leads to an understanding of this process would be of value. As working hypotheses, we propose a) that epithelial maintenance can be considered in relation to the control of three types of cellular activity; rates of synthesis, types of synthesis and establishment of tissue architecture and b) that a basic pattern of epithelial cell differentiation is continuously modulated by the subepithelial connective tissue into a site-specific pattern of organization. The objectives of the proposed research are to evaluate whether a) all epithelia have the same basic pattern of differentiation, b) there is a regional specificity of the connective tissue, c) epithelia are capable of remodulation, d) the organization, rate and time of epithelial synthesis are independently controlled and e) there is a specific cell type responsible for the role of maintaining epithelial integrity and specificity. To investigate these problems separation techniques have been developed to examine a selected, diverse range of oral epithelial and epidermal specimens following both homotypic and heterotypic recombination of epithelial and connective tissues transplanted to protected sites in histocompatible mice. The effects of such tissue interchanges on morphological structure, rates of cell production and patterns of synthesis of different types of keratin and cell surface materials are to be examined.